Flores-Villanueva P O, Yunis E J, Delgado J C, Vittinghoff E, Buchbinder S, Leung J Y, Uglialoro A M, Clavijo O P, Rosenberg E S, Kalams S A, Braun J D, Boswell S L, Walker B D, Goldfeld A E
Dana-Farber Cancer Institute, One Jimmy Fund Way, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5140-5. doi: 10.1073/pnas.071548198. Epub 2001 Apr 17.
Certain HLA-B antigens have been associated with lack of progression to AIDS. HLA-B alleles can be divided into two mutually exclusive groups based on the expression of the molecular epitopes HLA-Bw4 and HLA-Bw6. Notably, in addition to its role in presenting viral peptides for immune recognition, the HLA-Bw4, but not HLA-Bw6, motif functions as a ligand for a natural killer cell inhibitory receptor (KIR). Here, we show that profound suppression of HIV-1 viremia is significantly associated with homozygosity for HLA-B alleles that share the HLA-Bw4 epitope. Furthermore, homozygosity for HLA-Bw4 alleles was also significantly associated with the ability to remain AIDS free and to maintain a normal CD4 T cell count in a second cohort of HIV-1-infected individuals with well defined dates of seroconversion. This association was independent of the presence of a mutation in CC chemokine receptor 5 (CCR5) associated with resistance to HIV-1 infection, and it was independent of the presence of HLA alleles that could potentially confound the results. We conclude that homozygosity for HLA-Bw4-bearing B alleles is associated with a significant advantage and that the HLA-Bw4 motif is important in AIDS pathogenesis.
某些HLA - B抗原与艾滋病进展缓慢有关。根据分子表位HLA - Bw4和HLA - Bw6的表达情况，HLA - B等位基因可分为两个相互排斥的组。值得注意的是，除了在呈递病毒肽以供免疫识别方面发挥作用外，HLA - Bw4基序（而非HLA - Bw6基序）还作为自然杀伤细胞抑制性受体（KIR）的配体发挥作用。在此，我们表明，HIV - 1病毒血症的深度抑制与共享HLA - Bw4表位的HLA - B等位基因纯合性显著相关。此外，在第二组有明确血清转化日期的HIV - 1感染个体中，HLA - Bw4等位基因纯合性还与保持无艾滋病状态以及维持正常CD4 T细胞计数的能力显著相关。这种关联独立于与HIV - 1感染抗性相关的CC趋化因子受体5（CCR5）中的突变，并且独立于可能混淆结果的HLA等位基因的存在。我们得出结论，携带HLA - Bw4的B等位基因纯合性具有显著优势，并且HLA - Bw4基序在艾滋病发病机制中很重要。
